Diagnostic utility of serum or cerebrospinal fluid levels of toxic advanced glycation end-products (TAGE) in early detection of Alzheimer’s disease

Abstract

Alzheimer's disease (AD) is the most common cause of dementia in developed countries. AD is characterized pathologically by the presence of senile plaques and neurofibrillary tangles (NFTs), the major constituents of which are amyloid beta protein (A beta) and tau protein, respectively. Based on the disease pathology, numerous blood and cerebrospinal fluid (CSF) tests have been proposed for early detection of AD. However, there is no definite clinical method to determine in which patients with mild cognitive impairment will progress to AD with dementia. Therefore, to develop a novel promising biomarker for early diagnosis of AD is urgently needed. Several epidemiological studies have reported moderately increased risks for AD in diabetic patients compared with general population. In diabetes mellitus, the formation and accumulation of advanced glycation end-products (AGEs), senescent macroprotein derivatives, progress more rapidly. In addition, recent understanding of this process has confirmed that AGEs-their receptor (RAGE) interactions may play a role in the pathogenesis of neurodegenerative disorders including AD. In human AD brains, AGEs are distributed in the cytosol of neurons in the hippocampus and para-hippocampal gyrus. In this paper, we discuss the pathophysiological role for toxic AGEs (TAGE) in AD. We further review here the possibility that serum or cerebrospinal fluid levels of TAGE could become a promising biomarker for early detection of AD.